Tu Yinuo, Tian Yunhong, Wu Yinbing, Cui Shuzhong
Intracelom Hyperthermic Perfusion Therapy Center, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, Guangdong 510095, P.R. China.
Department of Radiation Oncology, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, Guangdong 510095, P.R. China.
Oncol Lett. 2018 Jun;15(6):9385-9391. doi: 10.3892/ol.2018.8508. Epub 2018 Apr 16.
Heat shock proteins (HSPs) are important factors in the response of cancer cells to thermo- and chemotherapy. Transient hyperthermic intraperitoneal chemoperfusion (HIPEC) therapy results in the upregulation of HSP expression, which may compromise the efficacy of additional anticancer treatments. The aim of the present study was to monitor the kinetics of HSP expression in tumor cells and patients with gastric cancer following HIPEC. Thus, and experiments were conducted to investigate the expression of two HSP family members, HSP70 and HSP90. Cells from two gastric tumor strains were subjected to HIPEC-mimicking treatment, and HSPs expression was analyzed at specific time points up to 48 h. Serum HSP concentrations were analyzed in patients with gastric cancer who had previously received cytoreductive surgery plus HIPEC treatment. The experiments indicated a significant elevation of HSP90 expression in gastric adenocarcinoma cells following hyperthermic treatment. However, HSP70 expression increased from 4 h up to 20 h post-exposure and decreased to normal levels 36 h post-exposure. Analysis of HSPs in serum samples collected from 22 patients with gastric cancer confirmed that serum HSP90 and HSP70 levels increased following HIPEC therapy, peaking at 18 h and returning to normal 24 h post-exposure. It is therefore advisable to apply the second round of HIPEC or chemotherapy at least 24 h following the first treatment to minimize any potential thermoresistance and chemoresistance of tumor cells.
热休克蛋白（HSPs）是癌细胞对热疗和化疗反应中的重要因素。短暂性腹腔内热灌注化疗（HIPEC）会导致HSP表达上调，这可能会削弱其他抗癌治疗的疗效。本研究的目的是监测HIPEC治疗后胃癌患者肿瘤细胞中HSP表达的动力学变化。因此，进行了实验以研究两种HSP家族成员HSP70和HSP90的表达情况。对两种胃癌细胞系进行模拟HIPEC治疗，并在长达48小时的特定时间点分析HSP的表达。对先前接受过肿瘤细胞减灭术加HIPEC治疗的胃癌患者血清中的HSP浓度进行分析。实验表明，热疗后胃腺癌细胞中HSP90的表达显著升高。然而，HSP70的表达在暴露后4小时至20小时升高，并在暴露后36小时降至正常水平。对22例胃癌患者采集的血清样本中的HSP进行分析证实，HIPEC治疗后血清HSP90和HSP70水平升高，在暴露后18小时达到峰值，并在暴露后24小时恢复正常。因此，建议在首次治疗后至少24小时进行第二轮HIPEC或化疗，以尽量减少肿瘤细胞的任何潜在热抗性和化学抗性。
